Making Labs-on-a-Chip Even Better

Lab-on-a-chip devices are emerging as convenient portable diagnostic solutions. But when one of those devices use an electric current during the diagnostic process, blood cells in the test sample can burst, causing inaccurate results. Engineers at Michigan Technological University are working on an elegant solution to fix that problem.

With advances in nanotechnology and microfluidics, lab-on-a-chip devices can perform tests using only a drop of blood and deliver immediate results. This makes them increasingly popular as diagnostic tools in rural areas for checking blood glucose levels, malaria, and blood types, as well as detecting the amount of white and red blood cells in a sample.

These tests are usually conducted by a combination of a few basic procedures, such as adding a specific reagent to detect color changes in the sample or applying an electrical field and observing how the blood cells react.

For example, the amount of glucose is deduced from an electrode-bound catalyst that selectively reacts with the glucose molecule, which then causes a release of electrons. The higher the number of glucose molecules, the more electrons are released, and a greater current flows through the circuit. This current is measured by the electrode to gauge the level of blood glucose.

Blood typing, on the other hand, is traditionally measured by agglutination reactions. Blood types are determined by the antigens in their membranes, and clump together when exposed to a specific antibody. By testing against different antibodies, clinicians can establish blood types quickly.

The Michigan Tech engineers have developed a novel approach that tracks the motion of the cells toward or away from the electrode upon application of a small electric current. It takes advantage of the different electrical properties of the membrane antigens that determine a blood cell’s type. Different antigens move through the microfluidic device at different speeds. The approach provides a simpler way to manipulate blood cells, the engineers said.

The problem is that when blood comes in contact with ions created from the micro-device electrodes, it can undergo lysis, which means the cells burst open. The antigen information that is coded on the cell is now scrambled and the integrity of the data sample is lost.

“Blood type is essentially characterized by a sugar molecule that’s on the membrane,” said principal investigator, Adrienne Minerick, professor of chemical engineering and dean of the School of Technology. “We want the cells intact. If they’re bursting apart in the electric field, then we can’t complete the test.”

The solution calls for is a thin 50 nm layer of hafnium oxide that essentially acts like a cellphone screen protector over the electrodes and prevents cell lysis. Hafnium oxide has several advantages: a high dielectric constant, which allows the electric field to reach the sample while imposing a physical barrier between the electrodes and sample; biocompatibility; and optical transparency, so developers can use it in tests that measure changes in color.

“Similar to touching your cellphone screen, the circuits beneath that cellphone protector can detect the signal,” Minerick said. “This coated lab-on-a-chip allows reactions to take place across this protective hafnium oxide layer.”

The devices have nanoscale features that the hafnium oxide layer adds molecule-by-molecule, through a process called radio frequency sputtering.

“RF sputtering starts with a piece of pure hafnium inside a vacuum chamber,” said Jeana Collins, a researcher on the project. The system then ionizes a mixture of inert argon gas and oxygen and directs it at the hafnium. When it hits, it ejects atoms into the vacuum, where they react with the ionized oxygen to form hafnium oxide and settle on the substrate on the other side of the vacuum chamber.

The processing conditions make a difference in the structure of the molecules and thickness. “It’s a bit like salt on the surface,” Minerick said. “If the crystals are loosely held, you can envision winding your way around those crystals [leaving gaps unprotected], but if you heated the salt and made it molten, it would flow, leading to better coverage.”

Collins and Minerick tested the hafnium oxide layers with average thicknesses of 58, 127, and 239 nm, as measured by spectroscopic ellipsometry. “Fifty to sixty nanometers was sufficient to prevent lysis,” Minerick said. “Over 120 nanometers and it is too thick to get electrical signals to go through.”

The solution is not without its headaches. The addition of the extra layer requires a little extra power to generate electric fields.

“It’s like you’re looking through goggles, so it distorts your sight and you can’t see as well,” Minerick said. “Fortunately, it’s not that much of an increase in power.”

The team tested other materials on the periodic table, but hafnium oxide proved to be the best contender.

“There are other ways of preventing cell lysis,” Minerick said. Another researcher in her team, doctoral candidate Sanaz Habibi, for example, is working on using low concentrations of a surfactant to provide a thin protective layer that would cushion the sample and prevent lysis.